Modular Engineered Hydrogels with Tailored Adhesive, Antibacterial, and Hemostatic Functions for Diverse Wound Healing Applications

Abstract Adapting multifunctional wound dressings to complex physiological environments remains a major clinical challenge. Herein, we report a modular polyacrylamide-co-acrylic acid N-hydroxysuccinimide (PAM-AA-NHS) hydrogel platform offering chemical versatility and mechanical tunability for precision care. To impart specific bio functionalities, adhesive-active functional materials, including tannic acid (TA), oxidized dextran (ODex), and catechol-conjugated chitosan (CHI-C), were individually incorporated into the hydrogel. TA-modified hydrogel demonstrated exceptional freeze-tolerant adhesion, retaining over 50% of its original adhesive strength at –20 °C and enabling effective wound healing under low-temperature conditions. ODex functionalization exhibited potent antibacterial activity (>95% inhibition), suggesting its potential for the management of infection-prone wounds. Furthermore, CHI-C-integrated hydrogel showed enhanced mechanical strength (tensile: 55.64 ± 3.71 kPa; compressive: 525.07 ± 13.80 kPa) and promoted erythrocyte aggregation via electrostatic interactions, achieving effective hemostasis under high-pressure bleeding conditions with blood loss reduced to 41.67 ± 4.11 mg in liver and 70.33 ± 6.60 mg in cardiac injury models. All hydrogel variants displayed favorable hemocompatibility, cytocompatibility, and significant in vivo wound healing performance. Collectively, this study presents a modular hydrogel system with tailored functional characteristics for diverse wound-management requirements, including low-temperature protection, antibacterial protection, and hemorrhage control.